scholarly journals Jian-Pi-Yi-Shen formula enhances perindopril inhibition of chronic kidney disease progression by activation SIRT3, modulation mitochondrial dynamics and antioxidant effects

2021 ◽  
Author(s):  
Xinhui Liu ◽  
Ruyu Deng ◽  
Xian Wei ◽  
Yuzhi Wang ◽  
Jiali Weng ◽  
...  

Chronic kidney disease (CKD) is a global public health problem. Renin–angiotensin system (RAS) blockade is the mainstay of CKD therapy with limitations. Jian-Pi-Yi-Shen formula (JPYSF) is a traditional herbal decoction and has been used for treating CKD for decades. The purpose of this study was to investigate the intervention effects of combined used of perindopril erbumine (PE) and JPYSF on CKD progression and explore their underlying mechanisms. CKD rat model was induced by feeding a diet containing 0.75% w/w adenine for 3 weeks. CKD rats were treated with PE or JPYSF or PE+JPYSF from the induction of CKD and lasted 4 weeks. Renal function was evaluated by serum creatinine and blood urea nitrogen. Pathological lesions were observed by periodic acid-Schiff and Masson’s trichrome staining. The protein expression was tested by Western blot and immunohistochemistry analysis. The morphology of mitochondria was observed by transmission electron microscope. The results showed that combined used of PE and JPYSF could better improve renal function and pathological lesions and ameliorate renal fibrosis in CKD rats. Administration of PE and JPYSF enhanced sirtuin 3 (SIRT3) expression, inhibited mitochondrial fission, promoted mitochondrial fusion, and suppressed oxidative stress in the kidney of CKD rats. In conclusion, combined use of PE and JPYSF protected against CKD more effectively than either alone. The underlying mechanism may be associated with activation of SIRT3, modulation of mitochondrial dynamics and antioxidant effects.

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Xinhui Liu ◽  
Shiying Huang ◽  
Fochang Wang ◽  
Lin Zheng ◽  
Jiandong Lu ◽  
...  

Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality. However, the therapies remain limited. Traditional Chinese medicine (TCM) has been used for treating kidney disease for thousands of years and is an effective alternative treatment for CKD patients in China and other Asian countries. In the present study, we aimed to investigate the effect and mechanism of Huangqi-Danshen decoction (HDD), a TCM herbal decoction, on treating CKD. CKD rat model was induced by adding 0.75% adenine to the diet for 4 weeks. HDD extract was administrated orally to CKD rats at the dose of 4.7 g/kg/d for consecutive 4 weeks in adenine-induced CKD rats. Kidney function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The pathological changes of kidney tissues were observed by periodic acid-Schiff (PAS) and Masson’s trichrome staining. The proteins expression of renal fibrosis and mitochondrial dynamics were determined and quantified by Western blot analysis. CKD rats showed obvious decline in renal function as evidenced by increased levels of Scr and BUN, which were blunted by HDD treatment. HDD could also improve tubular atrophy and interstitial fibrosis of CKD rats. Moreover, HDD downregulated fibronectin, type IV collagen, and α-smooth muscle actin expression in CKD rats. Furthermore, mitochondrial dynamics was disturbed in CKD rats, which manifested as increased mitochondrial fission and decreased mitochondrial fusion. HDD treatment restored mitochondrial dynamics in CKD rats by repressing dynamin-related protein 1 and Mid 49/51 expression, promoting mitofusin 2 expression, and suppressing optic atrophy 1 proteolysis. In conclusion, HDD could significantly retard CKD progression through modulating mitochondrial dynamics.


2021 ◽  
Vol 22 (9) ◽  
pp. 4480
Author(s):  
Maria Tziastoudi ◽  
Georgios Pissas ◽  
Georgios Raptis ◽  
Christos Cholevas ◽  
Theodoros Eleftheriadis ◽  
...  

Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. In an effort to elucidate the contribution of genetic variants located in several genes in the response to treatment of patients with CKD, we performed a systematic review and meta-analysis of all available pharmacogenetics studies. The association between genotype distribution and response to medication was examined using the dominant, recessive, and additive inheritance models. Subgroup analysis based on ethnicity was also performed. In total, 29 studies were included in the meta-analysis, which examined the association of 11 genes (16 polymorphisms) with the response to treatment regarding CKD. Among the 29 studies, 18 studies included patients with renal transplantation, 8 involved patients with nephrotic syndrome, and 3 studies included patients with lupus nephritis. The present meta-analysis provides strong evidence for the contribution of variants harbored in the ABCB1, IL-10, ITPA, MIF, and TNF genes that creates some genetic predisposition that reduces effectiveness or is associated with adverse events of medications used in CKD.


2018 ◽  
Vol 34 (11) ◽  
pp. 1853-1863 ◽  
Author(s):  
Ruifeng Wang ◽  
Titi Chen ◽  
Chengshi Wang ◽  
Zhiqiang Zhang ◽  
Xin Maggie Wang ◽  
...  

Abstract Background Chronic kidney disease (CKD) is a global public health problem, which lacks effective treatment. Previously, we have shown that CD103+ dendritic cells (DCs) are pathogenic in adriamycin nephropathy (AN), a model of human focal segmental glomerulosclerosis (FSGS). Fms-like tyrosine kinase 3 (Flt3) is a receptor that is expressed with high specificity on tissue resident CD103+ DCs. Methods To test the effect on CD103+ DCs and kidney injury of inhibition of Flt3, we used a selective Flt3 inhibitor (AC220) to treat mice with AN. Results Human CD141+ DCs, homologous to murine CD103+ DCs, were significantly increased in patients with FSGS. The number of kidney CD103+ DCs, but not CD103− DCs or plasmacytoid DCs, was significantly decreased in AN mice after AC220 administration. Treatment with AC220 significantly improved kidney function and reduced kidney injury and fibrosis in AN mice. AC220-treated AN mice had decreased levels of inflammatory cytokines and chemokines, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, CCL2 and CCL5 and reduced kidney infiltration of CD4 T cells and CD8 T cells. The protective effect of AC220 was associated with its suppression of CD103+ DCs-mediated CD8 T cell proliferation and activation in AN mice. Conclusion Flt3 inhibitor AC220 effectively reduced kidney injury in AN mice, suggesting that this inhibitor might be a useful pharmaceutical agent to treat CKD.


2013 ◽  
Vol 154 (2) ◽  
pp. 43-51 ◽  
Author(s):  
Judit Nagy

Chronic kidney disease is a general term for heterogenous disorders with >3 months duration affecting kidney structure and function. Nowadays, involving 10–16% of the adult population worldwide, chronic kidney disease is recognised as a major global public health problem. The number of cases is continuously increasing. In this review, epidemiology, definition, new classification and a conceptual model for development, progression and complications of chronic kidney disease as well as strategies to improve outcome are summarized. Orv. Hetil., 2013, 154, 43–51.


2021 ◽  
Vol 10 (11) ◽  
pp. 2255
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom

Chronic kidney disease (CKD), a damaged condition of the kidneys, is a global public health problem that can be caused by diabetes, hypertension, and other disorders. Recently, the MANBA gene was identified in CKD by integrating CKD-related variants and kidney expression quantitative trait loci (eQTL) data. This study evaluated the effects of MANBA gene variants on CKD and kidney function-related traits using a Korean cohort. We also analyzed the association of MANBA gene variants with kidney-related traits such as the estimated glomerular filtration rate (eGFR), and blood urea nitrogen (BUN), creatinine, and uric acid levels using linear regression analysis. As a result, 14 single nucleotide polymorphisms (SNPs) were replicated in CKD (p < 0.05), consistent with previous studies. Among them, rs4496586, which was the most significant for CKD and kidney function-related traits, was associated with a decreased CKD risk in participants with the homozygous minor allele (CC), increased eGFR, and decreased creatinine and uric acid concentrations. Furthermore, the association analysis between the rs4496586 genotype and MANBA gene expression in human tubules and glomeruli showed high MANBA gene expression in the minor allele carriers. In conclusion, this study demonstrated that MANBA gene variants were associated with CKD and kidney function-related traits in a Korean cohort.


Author(s):  
I. Dudar ◽  
I. Mykhaloiko

Chronic kidney disease (CKD) has become a global public health problem because of its high prevalence and the accompanying increase in the risk of end-stage renal disease, cardiovascular disease, and premature death. At present there is a number of experimental and clinical data that show that one of the important mechanisms of the pathogenesis of CKD is a violation of the blood coagulation system (hemostasis) both locally in the kidneys and with the capture of the microcirculatory channel of other organs, therefore an important task for specialists in the  nephrology, as well as doctors of other specialties is  understanding  the functioning of the system of hemostasis in normal and in various kidney diseases and the correction of this pathology with drugs. There are several types of haemostasis disorders that may occur in CKD: disseminated intravascular coagulation syndrome (DIC), arterial and venous thrombosis and bleeding. In this review, we tried to determine the place of the DIC in the development and progress of the CKD and to assess the prospects for further research.


2020 ◽  
Vol 10 (5) ◽  
Author(s):  
Sanam Dolati ◽  
Faezeh Tarighat ◽  
Fariba Pashazadeh ◽  
Kavous Shahsavarinia ◽  
Saina Gholipouri ◽  
...  

: Chronic kidney disease (CKD) is a global public health problem. Pain is one of the most generally experienced symptoms by CKD patients. Pain management is a key clinical activity; nonetheless, insufficient pain management by health professionals keeps it up. Opioids as pain relievers are a class of naturally-derived and synthetic medications. They act through interactions with receptors in peripheral nerves. Numerous pharmacokinetic alterations happen with aging that influence drug disposition, metabolism, and quality of life. Acetaminophen alone, or combined with low-potency opioid dose is regarded as the safest pain-relieving choice for CKD. Morphine and codeine are probably eluded in renal impairment patients and used with excessive carefulness. Tramadol, oxycodone, and hydromorphone can be used by patient monitoring, while methadone, transdermal fentanyl, and buprenorphine seem to be safe to use in older non-dialysis patients with renal impairment. Consistent with the available literature, the main aim of this review was to explore the occurrence of chronic pain and its opioid treatment in CKD patients. According to this review, more and well-made randomized controlled trials are necessary to find appropriate opioid doses and explore the occurrence of side effects.


Author(s):  
M. Kolesnyk

Chronic kidney disease (CKD) has become a global public health problem because of its high prevalence and the accompanying increase in the risk of end-stage renal disease, cardiovascular disease, and premature death. The role of uric acid (UA) in the pathogenesis and progression of CKD remains controversial. Although many evidence-based studies have suggested that UA itself may harm patients with CKD by increasing inflammation and CKD progression, the issue is still a matter of discussions. In this review we try to clarify what is hyperuricemia – cause of CKD, compensation, coincidence, consequence of CKD or it is only an epiphenomenon, and to evaluate current evidence of different types of targeted hypouricemic therapy effectiveness. So, to treat or not to treat?


2018 ◽  
Vol 21 (2) ◽  
Author(s):  
Mariusz Bodnar ◽  
Joanna Mazurkiewicz ◽  
Jacek Różański

Electrocardiographic changes of the nature of left ventricular hypertrophy with repolarization abnormalities may cause some diagnostic difficulties in the outpatient setting resulting from the etiology of changes. Chronic kidney disease (CKD) is a global public health problem that shortens lifespan, primarily by increasing risk of cardiovascular disease. Left ventricular hypertrophy (LVH) is a common pattern of cardiovascular injury in CKD that affects up to 75% of individuals by the time they reach end-stage renal disease. By promoting heart failure and atrial and ventricular arrhythmias, LVH is a powerful risk factor for cardiovascular events and death. The complex pathogenesis of LVH involves ventricular pressure and volume overload and the electrocardiographic record alone may sometimes suggest suspicion of an acute coronary syndrome. In this paper, we describe the case of a 39-year-old patient who was referred to the Cardiology Clinic with a preliminary diagnosis of „infarctus myocardia in evolution”, however, the final diagnosis was chronic kidney disease in stage 5 on a base of hypertensive nephropathy (not biopsy proven).


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