Treatment Of Chronic Renal Failure Research Articles

Integrated network analysis and experimental verification of the mechanisms employed by Compound Jixuecao Decoction to improve endoplasmic reticulum stress and apoptosis in chronic renal failure

Ethnopharmacological relevanceCompound Jixuecao Decoction (CJD) is a traditional Chinese herbal medicine prescribed in China to treat chronic renal failure (CRF). Previous studies have shown that CJD affects cell apoptosis and proliferation. However, the mechanism of its renal protective action has not been characterized. Aim of the studyTo explore the mechanism(s) underlying the effect of CJD on endoplasmic reticulum stress (ERS) and apoptosis in the treatment of CRF using network pharmacology, molecular docking, molecular dynamics simulations, and in vivo studies. Materials and methodsThe compounds comprising CJD were extracted from the Traditional Chinese Medicine Systems Pharmacology Database. A Swiss target prediction database and similarity integration approach were employed to identify potential targets of these components. The GeneCards and DisGeNET databases were used to identify targets associated with CRF, apoptosis, and ERS. The STRING database was employed to analyze the protein–protein interactions (PPIs) associated with drug–disease crossover. A chemical composition-shared target network was established, and critical pathways were identified through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The Protein Data Bank database was used to search key proteins, while molecular docking and dynamics simulations were performed between the top four CJD active ingredients and proteins involved in apoptosis and ERS in CRF. Subsequent in vivo studies using a 5/6 nephrectomy rat model of CRF were performed to verify the findings. ResultsThe 80 compounds identified in CJD yielded 875 target genes, of which 216 were potentially related to CRF. PPI network analysis revealed key targets via topology filtering. Enrichment analysis, molecular docking, and molecular dynamics simulation results suggested that CJD primarily targets mitofusin-2 (MFN2), B-cell lymphoma-2 (BCL2), BAX, protein kinase RNA-like ER kinase (PERK), and C/EBP homologous protein (CHOP) during CRF treatment. In vivo, CJD significantly increased the abundance of MFN2, BCL2, and significantly reduced the abundance of BAX, PERK, CHOP proteins in kidney tissues, indicating that CJD could improve apoptosis and ERS in CRF rats. ConclusionsThis study provides evidence that CJD effectively delays CFR through modulation of the MFN2 and PERK–eIF2α–ATF4–CHOP signaling pathways.

Study on the Chemical Composition and Blood-Entry Components of Nourishing Blood Diuretic Formula Based on Liquid Chromatography-Mass Spectrometry and Network Pharmacology Techniques

Objective: Analyzing the chemical composition and blood-entry components of Nourishing Blood Diuretic Formula (NBDF) by Liquid Chromatography-Mass Spectrometry (LC-MS), and analyzing the mechanism of NBDF in the treatment of chronic renal failure by combining network pharmacology and molecular docking technology. Methods: The prototype components were obtained by LC-MS, and the targets of the prototype components and the targets for the treatment of chronic renal failure (CRF) were predicted by network pharmacology to obtain the common targets of the drug and the disease, which were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and molecular docking was carried out between the compounds of the prototype components and the key targets, so as to screen out the active ingredients, the targets and the signaling pathways that were closely related to the efficacy of NBDF. Results: Synthesizing the test information, 125 compounds were identified from the solution of NBDF, and 48 blood-entry components were identified from rat plasma containing the drug, including 6 prototypical components, and 102 potential targets of action, 515 GO entries, and 133 KEGG pathways were obtained from the web-based pharmacological analyses, and molecular docking was performed to obtain the binding of the 6 prototypical component compounds and the 9 key targets, and the formononetin, emodin, epicatechin, chlorogenic acid, sennoside A, and astragaloside III were hypothesized to be the active components of NBDF in the treatment of CRF. Conclusion: This study initially demonstrated that Nourishing Blood and Diuretic Formula exert its therapeutic effects on CRF through multicomponents, multitargets, and multimethods, and elucidated its pharmacological material basis and therapeutic mechanism.

Effects of paricalcitol combined with hemodiafiltration on bone-metabolism-related indexes in patients with diabetic nephropathy and chronic renal failure.

Diabetic nephropathy (DN) is frequently seen in the development of diabetes mellitus, and its pathogenic factors are complicated. Its current treatment is controversial, and there is a lack of a relevant efficacy prediction model. To determine the effects of paricalcitol combined with hemodiafiltration on bone-metabolism-related indexes in patients with DN and chronic renal failure (CRF), and to construct an efficacy prediction model. We retrospectively analyzed 422 patients with DN and CRF treated in Cangzhou Central Hospital between May 2020 and May 2022. We selected 94 patients who met the inclusion and exclusion criteria. Patients were assigned to a dialysis group (n = 45) and a joint group (n = 49) in relation to therapeutic regimen. The clinical efficacy of the two groups was compared after treatment. The changes in laboratory indexes after treatment were evaluated, and the two groups were compared for the incidence of adverse reactions. The predictive value of laboratory indexes on the clinical efficacy on patients was analyzed. The dialysis group showed a notably worse improvement in clinical efficacy than the joint group (P = 0.017). After treatment, the joint group showed notably lower serum levels of serum creatinine, uric acid (UA) and blood urea nitrogen (BUN) than the dialysis group (P < 0.05). After treatment, the joint group had lower serum levels of phosphorus, procollagen type I amino-terminal propeptide (PINP) and intact parathyroid hormone than the dialysis group, but a higher calcium level (P < 0.001). Both groups had a similar incidence of adverse reactions (P > 0.05). According to least absolute shrinkage and selection operator regression analysis, UA, BUN, phosphorus and PINP were related to treatment efficacy. According to further comparison, the non-improvement group had higher risk scores than the improvement group (P < 0.0001), and the area under the curve of the risk score in efficacy prediction was 0.945. For treatment of CRF and DN, combined paricalcitol and hemodiafiltration can deliver higher clinical efficacy and improve the bone metabolism of patients, with good safety.

Efficacy of Jinshuibao as an adjuvant treatment for chronic renal failure in China: A meta-analysis.

Research on Jinshuibao (JSB) for chronic renal failure (CRF) is limited, its clinical efficacy on CRF has not been evaluated. Our aim is to systematically evaluate the efficacy of JSB for the treatment of CRF in Chinese patients, and to provide evidence-based medical advice for clinical practice. Randomized controlled trials (RCTs) which compared JSB combined with conventional treatment (CT) with CT alone in CRF were searched in 8 databases including PubMed, EMBASE, Cochrane Library, Web of science, China Biology Medicine disc, Wanfang, Chinese Scientific Journal Database (VIP) and China National Knowledge Infrastructure form inception to March 31, 2023. RevMan5.4 statistical software was used for meta-analysis. 17 trials involving 1431 cases were identified for meta-analysis. The results showed that total effective rate (relative risk [RR] = 1.25, 95% confidence internal [CI]: 1.17-1.34, P < .00001), creatinine clearance rate (Ccr) (MD = -8.63, 95% CI: -12.42 to -4.84, P < .00001), albumin (Alb) (MD = -2.88, 95% CI: -4.85 to -0.92, P = .004) and hemoglobin (Hb) (MD = -5.88, 95% CI: -7.42 to -4.34, P < .00001) in JSB plus CT were significantly higher than those in CT; while blood urea nitrogen (BUN) (MD = 2.03, 95% CI: 1.27-2.80, P < .00001), serum creatinine (Scr) (MD = 48.23, 95% CI: 31.96-64.49, P < .00001), 24-hour urine protein (24hpro) (MD = 0.19, 95% CI: 0.06-0.31, P = .003), uric acid (UA) (MD = 76.36, 95% CI: 12.40-140.31, P = .02), tumor necrosis factor-α (TNF-α) (MD = 10.74, 95% CI: 5.04-16.45, P = .0002), interleukin-6 (IL-6) (MD = 5.07,95% CI: 1.21-8.92, P = .01), high-sensitivity C-reactive protein (hs-CRP) (MD = 3.74, 95% CI: 0.96-6.52, P = .008) in JSB plus CT were significantly lower than those in CT. Combining JSB with CT has a good effect on the treatment of CRF in Chinese people. High-quality RCTs are needed to further confirm the results.

Effect of Salvia miltiorrhiza Combined with Aromatic Amino Acids on the Impaired Renal Function in Rats with Chronic Renal Failure

Background and Aim: At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Salvia miltiorrhiza (SM) is a very popular medicinal plant that has been extensively applied to treat various diseases. It also has been reported that lowering the aromatic aminoacids (AAA) in the protein diet can improve renal function in rodents with CRF. This study seeks to employ the use of SM combined with low aromatic amino acid diet (LA-AAD) for treatment of CRF in rats. Methods: Animals were assigned into 3 groups: Control, CRF and Experiment. CRF models were induced by 2.5% adenine administered by gavage for 8 weeks. Control and CRF group received normal protein diet (18.8% proteins, AAA 0.024%), and Experiment group was divided into 3 subgroups, being treated with SM (1.0g/kg/d) and LA-AAD (18% proteins, AAA 0.009%) differently. Proteinuria, blood urine nitrogen (BUN), serum and urine creatinine (Scr, Ucr) were measured and creatinine clearance rate (CCR) was calculated accordingly. Results: Proteinuria, BUN, Scr analyses showed amelioration of functional parameters and increased the CCR significantly in LA-AAD + SM group. Conclusion: These results showed that the combination of SM and LA-AAD could be beneficial to the improvement of renal function in CRF rats and this method can be a novel strategy for CRF treatment.

Neoxanthin alleviates the chronic renal failure-induced aging and fibrosis by regulating inflammatory process.

Chronic renal failure (CRF) refers to progressive renal damage caused by chronic kidney diseases (CKD). Dialysis therapy and kidney transplantation are the important treatment for CRF. However, due to the limitation of conditions, they cannot be widely utilized. At present, the treatment of renal failure is a worldwide problem in clinic. Therefore, in the current study, we investigated the potential therapeutic effects of neoxanthin on CFR-caused aging and fibrosis. In this work, the effects of neoxanthin on CRF were studied using experimental techniques such as biochemistry, immunohistochemistry and molecular biology. In vitro, neoxanthin alleviated the aging and oxidative damage of kidney cells. In vivo, we found that Neoxanthin could alleviate adenine-induced CRF. Neoxanthin also inhibited CRF-caused renal aging, fibrosis, oxidative stress and inflammation. These findings indicate that neoxanthin could delay the progression of CRF and alleviate CRF-induced aging and fibrosis. Collectively, we found that neoxanthin shows good potential to inhibit CRF-caused kidney aging and fibrosis, suggesting that neoxanthin may be used as a drug (or a functional food) for the treatment of CRF-related diseases.

Biochemical and histopathological evaluations of chronic renal failure rats treated with pluripotent human stem cells

Regeneration of damaged kidney cells using stem cells is the current research approach in the treatment of chronic renal failure (CRF). In the present study, the histopathological and biochemical techniques were used to evaluate stem cells’ (SCs) role in treatment of CRF. Sixty-four rats were divided into eight groups. Group I (GI): rats were injected with doxorubicin (15 mg/kg) to initiate CRF. GII-GVII: rats were injected with doxorubicin and treated with SCs (1x106 MSCs or/and 2x104 HSCs/rat) with/without growth factors extract (200 µL/rat) and/or immunosuppressor (cyclosporine A, 5 mg/kg/day). GVIII: rats treated with PBS (100 µL/kg/day). Levels of creatinine, urea and uric acid were increased in rats sera after injection with doxorubicin, while blood electrolyte levels of Na, K, P and Mg were decreased. Also, histopathological abnormalities such as hyalinized blood vessels, degenerated hyalinized glomerulus tubules and cell debris in the lumen and degeneration of renal tissues were observed in these rats. After treatment with SCs, all these parameters restore their normal values with regeneration of the damaged cells as demonstrated in histopathology of the treated groups. It can be concluded that, the use of SCs in treatment of kidney diseases is a promising approach and needs more efforts.

Efficacy and safety of colonic dialysis combined with traditional Chinese medicine retention enema in the treatment of chronic renal failure: A protocol for systematic review and meta-analysis.

Background:Chronic renal failure (CRF) is a major public health problem worldwide nowadays. It is characterized by a slow reduction in kidney function identified by an increase of serum creatinine levels and a reduction of urine output. CRF is easier to diagnose than to treat. Clinical evidence shows that colonic dialysis combined with traditional Chinese medicine (TCM) enema can treat CRF by reducing serum creatinine. To assess the therapeutic efficacy and safety of colonic dialysis combined with Traditional Chinese medicine retention enema in CRF, we created a protocol for a systematic review to inform future clinical applications.Methods:Eligible random controlled trials were collected from 8 bibliographic databases (PubMed, EMBASE, Web of Science, The Cochrane Library, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Wanfang Database), completed before October 2021. The primary outcome is the serum creatinine, Urea nitrogen, total effective rate, uric acid, creatinine clearance. Secondary outcome: TCM syndrome score, glomerular filtration rate, hemoglobin, adverse reactions, and adverse events. Data extraction and quality assessment were independently conducted by 2 researchers. The quality and bias of the data were assessed using RevMan5.4 software.Results:This study will provide a clinical basis for colonic dialysis combined with TCM retention enema in the treatment of CRF.Conclusion:Colonic dialysis combined with TCM retention enema in the treatment of CRF can delay the progression of renal disease, proving its effectiveness and safety.INPLASY Registration number:INPLASY2021100116

The Dysregulation of Eicosanoids and Bile Acids Correlates with Impaired Kidney Function and Renal Fibrosis in Chronic Renal Failure

Chronic renal failure (CRF) is an irreversible deterioration of the renal functions that characterized by fluid electrolyte unbalance and metabolic-endocrine dysfunctions. Increasing evidence demonstrated that metabolic disturbances, especially dyslipidemia and profound changes in lipid and lipoprotein metabolism were involved in CRF. Identification of lipids associated with impaired kidney functions may play important roles in the understanding of biochemical mechanism and CRF treatment. Ultra-performance liquid chromatography coupled with high-definition mass spectrometry-based lipidomics was performed to identify important differential lipids in adenine-induced CRF rats and investigate the undergoing anti-fibrotic mechanism of Polyporus umbellatus (PPU) and ergone (ERG). Linear correlation analysis was performed between lipid species intensities and creatinine levels in serum. Adenine-induced rats exhibited declining kidney function and renal fibrosis. Compared with control rats, a panel of lipid species was identified in the serum of CRF rats. Our further study demonstrated that eight lipids, including leukotrienes and bile acids, presented a strong linear correlation with serum creatinine levels. In addition, receiver operating characteristics analysis showed that eight lipids exhibited excellent area under the curve for differentiating CRF from control rats, with high sensitivity and specificity. The aberrant changes of clinical biochemistry data and dysregulation of eight lipids could be significantly improved by the administration of PPU and ergone. In conclusion, CRF might be associated with the disturbance of leukotriene metabolism, bile acid metabolism and lysophospholipid metabolism. The levels of eicosanoids and bile acids could be used for indicating kidney function impairment in CRF. PPU could improve renal functions and either fully or partially reversed the levels of eicosanoids and bile acids.

Detection technology for activation and release of granular membrane protein

The purpose of this study was to investigate changes in plasma endothelin, platelet granule membrane protein and anticoagulant protein. In addition, the mechanism of action between blood stasis syndrome of chronic renal failure (CRF) and granule membrane protein was analyzed, and the relationship between activation release detection technology and blood stasis syndrome was discussed. There were significant differences in endothelin (ET), granule membrane protein-140 (GMP-140) and ceruloplasmin (CP) between the group with severe CRF and the group with mild CRF (P &lt; 0.01). The blood stasis syndrome of CRF was positively correlated with ET and GMP-140 and negatively correlated with CP, which indicated that ET, GMP-140 and CP were some of the objective indexes for the diagnosis and treatment of CRF. Based on the theory of the treatment of CRF with a combination of traditional Chinese and Western medicine at the molecular level, this paper provides a new basis for the treatment of CRF with blood stasis syndrome.

KMUP-1 regulates the vascular calcification in chronic renal failure by mediating NO/cGMP/PKG signaling pathway

ObjectiveTo explore the potential mechanism of KMUP-1 in the vascular calcification of chronic renal failure (CRF) through mediating NO/cGMP/PKG pathway, and provide novel insights into the CRF treatment. MethodsCRF rats were treated by KMUP-1 with/without L-NNA (a NOS inhibitor) and then performed by ELISA, alizarin red staining, Von Kossa staining, Masson's trichrome, Sirius red staining and CD3 immunohistochemical staining. Simultaneously, vascular smooth muscle cells (VSMCs) were collected from rats to confirm the effect of KMUP-1 on vascular calcification in vitro via NO/cGMP/PKG pathway. Besides, protein and mRNA expressions were determined via Western blotting and qRT-PCR, respectively. ResultsCRF rats were elevated in 24-h urine protein, blood urea nitrogen (BUN), serum creatinine, Cys-C levels and inflammatory cytokines. Besides, CRF rats also showed increased calcium content and ALP level with up-regulated mRNA of osteogenic differentiation-related markers. Furthermore, the up-regulated expressions of eNOS and PKG, as well as down-regulated levels of NOx and cGMP were also found in CRF rats. However, renal failure and vascular calcification of CRF were improved significantly by KMUP-1 treatment via activation of NO/cGMP/PKG pathway. Moreover, KMUP-1 treatment attenuated calcified VSMCs, accompanied by the decreases in the calcified nodules, level of calcium and activity of ALP. In addition, either L-NNA treatment for CRF rats or the calcified VSMCs could antagonize the improving effect of KMUP-1. ConclusionKMUP-1 can improve the renal function and vascular calcification in CRF rats at least in part by activating NO/cGMP/PKG pathway.

Inhibitory effect of Ginkgo biloba extract on vascular calcification in rats with chronic kidney disease by ROS-NF-κB signaling pathway

In order to explore the mechanism of Extract Gingko biloba (EGb761) inhibiting vascular calcification in rats with chronic kidney disease (CKD) through ROS-NF-κB signaling pathway, adult male healthy SD (Sprague Dawley) rats were selected as the research objects. Animal models were constructed and randomly divided into control group, high phosphorus-induced residual renal vascular calcification model group (HPIAC group), and EGb761 intervention calcification group. Samples were collected from each group of rats, and the renal function, aortic calcification, and the expression of related proteins were detected by Western blot. The results showed that the contents of urea nitrogen, creatinine, and phosphorus in calcification model group increased significantly, with significant statistical difference (P < 0.05), but did not decrease significantly after intervention with EGb761. In the comparative analysis of calcium content in aorta of rats in each group, it was found that the calcium content of abdominal aorta in model group was significantly higher than that in control group. After the intervention of EGb761, the calcium content of abdominal aorta was significantly decreased, with significant statistical difference (P < 0.05). Western blot was used to detect the expression levels of NF-κB (nuclear factor-κB) P65, cbfα1 (core binding factor-α1), and α-SM (a-smooth muscle) actin in thoracic aorta of rats in each group. It was found that the expression levels of NF-κB p65 and cbfα1 in thoracic aorta of rats in HPIAC group increased significantly, while the expression of α-SM actin decreased significantly, with significant statistical difference (P < 0.05). After the intervention of EGb761, the change of the protein was alleviated obviously, with significant statistical difference (P < 0.05). Therefore, through this study, it was found that EGb761 can partially alleviate the calcification of chronic renal failure (CRF) caused by high phosphorus by interfering with the expression of NF-κB p65 protein in rat thoracic artery. Although there are some shortcomings in the experiment, it still provides experimental basis for the treatment of CRF in the later clinical stage.

Effect of Bailing capsule on cellular immunity and renal function in patients with chronic renal failure CKD3-4

Objective To investigate the effect of Bailing capsule in the treatment of chronic renal failure (CRF). Methods A total of 120 patients with chronic renal failure CKD 3-4 who were admitted to Longhua hospital affiliated to Shanghai university of Chinese Medicine from January 2018 to May 2018 were randomly divided into control group and experimental group(n=60). The control group was given dietary control to regulate blood pressure, blood lipids, blood sugar. to correct anemia, improve acid-base imbalance and electrolyte imbalance, and the experimental group was given Bailing capsule on the basis of the control group. Continuous treatment for 3 months, comparing the total effective rate and renal function levels of the two groups, including serum creatinine (Scr), urea nitrogen (BUN), creatinine clearance (Ccr), T lymphocyte subsets and cytokine levels, including CD3+, CD4+, CD4+/CD8+, natural killer(NK) cells. Results The total effective rate of the experimental group after treatment was higher than that of the control group, and the difference was statistically significant (P 0.05). The renal function levels (Scr, BUN) of the two groups were better than those before treatment, and the experimental group was better than the control group, the difference was statistically significant (P<0.05). The level of Ccr after treatment was higher than that before treatment, and the experimental group was higher than the control group, the difference was statistically significant (P<0.05). The CD3+, CD4+, CD4+/CD8+, and natural killer (NK) cells were increased in the two groups after treatment. The difference between the two groups was statistically significant (P<0.05), and the experimental group had high T lymphocyte subsets. In the control group, the difference was statistically significant (P<0.05). Conclusions Bailing capsule has a good clinical effect in the treatment of CRF, which can improve renal function and enhance immune function. It has certain clinical application value. Key words: Kidney Failure, Chronic; CHINESE PATENT DRUGS

SUN-004 THE REGULATION OF THE GUT-KIDNEY AXIS IN VIVO BY TOTAL FLAVONE OF ABELMOSCHUS MANIHOT, A NATURAL EXTRACT, CONTRIBUTES TO THE AMELIORATION OF ADENINE-INDUCED RENAL FAILURE

Targeting gut microbiota dysbiosis and uremic toxins accumulation is important for the amelioration of renal dysfunction in chronic renal failure (CRF). Total flavone of abelmoschus manihot (TFA), a natural extract, has been applied extensively for treatment of the CRF patients in China. However, its therapeutic mechanisms remained elusive. Therefore, in this study, using an adenine-induced renal failure (RF) rat model, we examined the effects of TFA on the gut-kidney axis in vivo, compared with lubiprostone (LUB), then to clarify the potential mechanisms. Rats were randomly divided into 4 groups, the Sham-operated group, the Vehicle-given group, the TFA-treated group and the LUB-treated group. TFA, LUB and saline were daily administrated for 4 weeks after induction of RF by adenine gavage with unilateral ureteral obstruction (UUO). Renal injurious and dysfunctional indicators, tubulointerstitial fibrosis (TIF), fecal microbiota, gut-derived uremic toxins, colon histological characteristics and tight junction proteins expressions, as well as the key protein expression levels of TLR4/NF-κB/NLRP3 inflammasome pathways in the colon and the kidneys were examined, respectively. In the RF model rats, in addition to renal lesions and uremic toxins accumulation, the abundance of Lactobacillus in the gut was decreased, while that of C. perfringens in the gut was increased; There appeared the ulcers in the colon, accompanied with the low-expression of ZO-1 and claudin-1; Besides, TLR4/NF-κB/NLRP3 inflammasome pathways in the colon and the kidneys were activated, respectively. After the treatment of TFA or LUB, renal dysfunction and TIF in the RF model rats were significantly improved. Furthermore, the disordered Lactobacillus, Enterococcus, E. coli and C. perfringens in the gut, the damaged intestinal environment and the accumulative indoxyl sulfate and p-cresyl sulfate in serum were all ameliorated. More notably, TFA synchronously inhibited TLR4/NF-κB/NLRP3 inflammasome pathways activity in the colon and the kidneys, whereas, LUB only suppressed TLR4/NF-κB/NLRP3 inflammasome pathway activity in the colon. TFA, as a natural regulator in vivo, regulates the gut-kidney axis and ameliorates renal dysfunction in the RF model rats by modulating gut microbiota, reducing uremic toxins and inhibiting TLR4/NF-κB/NLRP3 inflammasome pathways activity in the colon and the kidneys, which is different from LUB. These findings may provide the first evidence for the gut-kidney axis, as the unusual target of TFA treatment in CRF.

ITRAQ-Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha-1-Antitrypsin as Potential Biomarkers.

Background. Chronic renal failure (CRF) has become a global health problem and bears a huge economic burden. FuShengong Decoction (FSGD) as traditional Chinese medicine has multiple pharmacological effects. Objectives. To understand the underlying molecular mechanism and signaling pathway involved in the FSGD treatment of CRF and screen differentially expressed proteins in rats with CRF treated with FSGD. Methods. Thirty-three male Sprague-Dawley rats were randomly divided into control group, CRF group, and FSGD group. Differentially expressed proteins were screened by iTRAQ coupled with nanoLC-MS/MS, and these identified proteins were later analyzed by GO, KEGG, and STRING. Additionally, haptoglobin (HP) and alpha-1-antitrypsin (AAT) were finally verified by ELISA, Western blot, and real time PCR. Results. A total of 417 proteins were identified. Nineteen differentially expressed proteins were identified in the FSGD group compared with the model group, of which 3 proteins were upregulated and 16 proteins were downregulated. Cluster analysis indicated that inflammatory response was associated with these proteins and complement and coagulation cascade pathways were predominantly involved. The validation methods further confirmed that the levels of HP and AAT were significantly increased. Conclusions. HP and AAT may be the important biomarkers in the pathogenesis of CRF and FSGD therapy.

THE PROTEIN METABOLISM IN SMALL ANIMALS WITH CHRONIC RENAL FAILURE AND ITS CORRECTION

Chronic renal failure (CRF) is often diagnosed in cats and dogs of old age. CRF is a consequence of metabolic deviations because of diseases (for example, generalized atherosclerosis, hypertensive disease, diabetes and others) and incorrect feeding. CRF is also a result of the delayed diagnosis of diseases of the urinary system and/or inadequate treatment. Aim of research. To study the biochemical parameters of protein metabolism that are important for determination of CRF stages and sub-stages in old small animals during correction of metabolic deviations. Materials and methods. There were analyzed biochemical indices (creatinine concentration in the blood serum; the ratio of protein/creatinine (UP/C) in the urine) and measured arterial blood pressure in 5 cats and 5 dogs with chronic renal failure selected from patients of the clinic according to medical history, clinical examination and special analysis. Results. It was analyzed CRF stages and sub-stages classification according to the International Renal Interest Society (IRIS). According to the date of creatinine concentration in the blood serum, CRF of the second stage was observed in 5 cats (140-250 μmol/L) and 3 dogs (125-180 μmol/L), and of the third stage - in 2 dogs (181-440 μmol/L). The CRF sub-stage as «without proteinuria» (UP/C &lt; 0.2) was identified in 1 cat, «marginal proteinuria» (UP/C 0.2-0.4) – in 1 cat and «proteinuria» (UP/C &gt; 0.4) - in 3 cats, and as «proteinuria» (UP/C &gt; 0.5) - in 5 dogs. Conclusions. An important step of the successful treatment of CRF is the definition of the stages and sub-stages according to IRIS based mostly on the measurements of biochemical indices in the blood and urine of sick animals ‒ indicators of creatininemia and proteinuria, a change of which was caused mainly by metabolic processes of proteins under influence of exogenous factors (the traditional treatment of CRF plus enalapril and diet nutrition).

Neurobehavioral Alterations and Brain Creatine Kinase System Changes in Chronic Renal Failure Induced Male Wistar Rats: Impact of Erythropoietin Supplementation

Chronic renal failure (CRF) is a rapidly growing global health problem and it causes anaemia and cognitive impairment. Recombinant Human erythropoietin (rHu-Epo) has been a promising role in the management of anaemia in CRF subjects and it is well documented. It also shown as a remarkable neuroprotection in both cell cultures and in animal models. Creatine kinase (CK) plays a key role in energy metabolism and its activity found in cytoplasm of several human tissues; major sources of CK include skeletal muscle, myocardium and brain. Studies show brain energy metabolism is key to neuronal cell function and cognitive health. The aim of this study is to investigate the impact of rHu-Epo on CRF induced changes in CK system in serum and brain regions of experimental animals and to test its significance in neurobehavioral changes. Experimental design is divided into two phases to find out the variation between simultaneous and post rHu-Epo Treatment in CRF induced male wistar rats. At the end of 40 days, animals were sacrificed uniformly. In both phases, CK level in serum and selected brain regions such as cerebellum, cerebral cortex and hippocampus were determined by spectrophotometric method and hematological parameters (RBC, Hb, PCV, MCV, MCH, MCHC) were also determined. In results, decreased creatine kinase activity in brain regions and its increased level in serum observed in CRF induced animals. Neurobehavioral changes and alterations in hematological parameters were also seen in CRF induced animals. Supplementation of rHu-Epo in both simultaneous and post treatment group reversed the CRF induced changes including neurobehavioral alterations, significantly. In this study, the protective role of Epo supplementation on CRF induced changes in CK system in both brain and serum and its correlation with neurobehavioral changes were seen along with its antianemic effect.

ANALYSIS OF COST AND OUTCOME THERAPY OF BLOOD TRANSFUSION ON ANEMIA TREATMENT FOR INPATIENT WITH CHRONIC RENAL FAILURE

Chronic Renal Failure (CRF) is a slow progressive loss of kidney function over a period of several years. One of its complications that determines the patient’s quality of life is anemia. Blood transfusion can be used to treat anemia in patient with CRF. The purpose of this study are to measure the average costs per patient, assess the therapy outcomes, and determine the factors that influence the cost of blood transfusion in anemia treatment for patients with CRF in A, B, and C hospitals. This study was a descriptive non-experimental research. Cost analysis was based on the perspective of the hospital. Data were obtained retrospectively from medical records and payment details of inpatient with CRF who experienced anemia in A (tertiery hospital in Yogyakarta province), B (tertiary hospital in Central Java province), and C (private hospital in the province of Yogyakarta) hospitals. Data was analysed by calculating the average costs per patient, while therapy outcome was measured by calculating the percentages of patients who achieved the target of hemoglobin level. Furthermore, the factors that influenced the amount of the total cost were analysed using Oneway ANOVA and Independent T-Test for data with normal distribution and the Kruskal-Wallis and Mann-Whitney for data with non-normal distribution. The results showed that the average costs per patient for anemia treatment in patient with CRF who had blood transfusion therapy were Rp 8,873,243.39±4,417,825.83 in A hospital, Rp 5,249,464.97±4,283,655.41 in B hospital; and Rp 7,961,088.00±6,105,501.80 in C hospital. Most of the patients in A, B, and C hospitals had achieved the target of hemoglobin level (>7g/dL) with the percentages of 95.56%, 68.57% and 87.50% respectively. The factors that mainly influenced the cost of anemia treatment in CRF are length of hospitalization for A hospital, age, gender, payment models, and length of hospitalization for B hospital, whereas age and length of hospitalization for C hospital. Key words : cost analysis, outcome therapy, blood transfusion, anemia, chronic renal failur

Presurgical pulmonary evaluation in renal transplant patients.

Patients with chronic renal failure (CRF) due to various mechanisms are prone to significant pulmonary comorbidities. With the improvements in renal replacement therapy (RRT), patients with CRF are now expected to live longer, and thus may develop complications in the lung from these processes. The preferred treatment of CRF is kidney transplantation and patients who are selected to undergo transplant must have a thorough preoperative pulmonary evaluation to assess pulmonary status and to determine risk of postoperative pulmonary complications. A MEDLINE®/PubMed® search was performed to identify all articles outlining the course of pre-surgical pulmonary evaluation with an emphasis on patients with CRF who have been selected for renal transplant. Literature review concluded that in addition to generic pre-surgical evaluation, renal transplant patients must also undergo a full cardiopulmonary and sleep evaluation to investigate possible existing pulmonary pathologies. Presence of any risk factor should then be aggressively managed or treated prior to surgery.

Evaluation of the cognitive functions in patients with chronic renal failure before and after renal transplantation

Chronic renal failure (CRF) and dialysis treatment affect central nervous system and studies have shown that neurocognitive dysfunctions are caused by CRF and dialysis treatment. The aim of this study was to evaluate the changes in cognitive functions of CRF patients after renal transplantation. Neurocognitive functions of 40 renal transplantation patients aged 18-65years were determined before, 6 and 12months after transplantation between 2008 and 2010 using neuropsychological tests. Rey Auditory-Verbal Learning Test (RVLT), Rey Complex Figure Test (RCFT), ADAS-cog Test, Stroop Test (ST), Digit Span Test (DST), and Trail Making Test (TMT) were applied. The test results were statistically compared taking into consideration the patients' levels of education, age, gender, donor type, duration of dialysis, dialysis type, and duration of CRF. Neuropsychological test results statistically significantly increased in all the patients after renal transplantation (p<0.05). The female patients' RVLT test results were statistically higher than the test results of the male patients (p<0.05). DST, RCFT, RVLT, and (Verbal Fluency Test) VFT results were statistically higher in the patients who were 33 years old or younger (p<0.05). The patients with high school and college education had statistically significantly higher results in all the tests when compared with the patients that were elementary school graduates (p<0.05). DST forward task, ST, and RVLT results of the patients, who had received dialysis treatment for 1year or less, were found to be statistically higher than the results of the patients who had received dialysis for more than 1year (p<0.05). The results of RCFT, RVLT, DST backward task, and VFT were statistically higher in the peritoneal dialysis patients than in the hemodialysis patients (p<0.05). The donor type and the duration of CRF had no significant effects on the results (p>0.05). The results of this study showed significant improvement in attention, memory, executive functions, pace of data processing and language functions in CRF patients after renal transplantation, as proven with neuropsychological tests.